Amino-carboxylic acid esters of monoglycerides



Patented Aug. 27, 1946 2,406,329 AMINO-CARBOX YLIC ACID ESTERS OF MONOGLYCERIDES Benjamin R. Harris, Chicago, n1.

No Drawings This invention relates to the preparation of new chemical compounds which are especially useful for antiseptic, medicinal, preservative, bactericidal, bacteriostatic, germicidal and fungicidal purposes. ,7 W H At least many of the novel substances oithe present invention, which, in use, are employed particularly in the form of salts such as hydrochlorides, as hereinafter set forth, fall within the scope of the general formula:

V CHr-CR 0110 R eHr-o-c-x wherein 0 H R-C is an acyl radical,

0 ll XO-- is th acyl radical of an amino carboxylic acid containing at least one primary amino group, and R. is hydrogen or the acyl radical of an amino-carboxylic acid.

The novel substances of the present invention, generally used in the form of their salts as indicated hereinabove, may be regarded as amino- ,carboxylic acid esters of monoglycerides, particularly monoglycerides of higher molecular weight fatty acids, especially satisfactory being those derived from fatty acids containing from eight to fourteen carbon atoms.

In order that the nature of the invention may become more apparent, there are listed hereinbelow various of the novel substances which generally are used in the form of salts, especially, hydrochlorides, and fall within the scope of the invention:

Application February 5, 1941, Serial No. 377,487

3 Claims. (Cl. 260-404) HOE 1 erq-esaecn cn-cm 1 NH: CH:

The substances are; prepared, preferably, by

converting the amino-carboxylic acid into its acyl chloride or a salt of its acyl chloride, uch as the I hydrochloride, and reacting the same with the a stoichiometric equivalent of the .monoglycerider V i The following examples are illustrative of a method which has been found suitable for preparingthe various compounds which ar disclosed herein. It will be appreciated that other methods may .be utilized, that the proportions of reacting l art in the light of the guiding-principleswhich are disclosed herein.

Example A 5.4 grams of monostearin;(containing approxi mately 96.8% of monostearin and 3.2% of free stearic acid) were dispersed in 35jcc. of -chloro-.

solution there were added 5.1 grams of thehydrm chloride of alpha-amino isobutyryl chloride. A

4 0., hydrochloric acid gas being evolved, and then I the mixture was heated for hour at 80-100 degrees C. at which time ver little hydrochloric acid gas was evolved. Th hydrochloric acid gas and chloroform wer then. removed from the reaction mixture by heating at 100 degrees C. under reduced pressure. The residue was then extracted twicecwith 50 =cc; portions of; hot 'ac'eto'ne; The acetone extract was evaporated to dryness under 1 0 reduced pressure. The product was dispersibl in i isopropanoLacetoneand petroleum ether. It was recoveredJrom-a mixture of these solvents by evap,oration under reduced pressure. A white,

waxy solid was obtained which was dispersible in 5. ':-water.f 'Il'ie= :reaction mass contained a slight amount of ,nnreacted stearic acid, some monolstearinl and' a mixture of the hydrochlorides of the ih'onoand di-esters of alpha amino-isoi" butyri'iacid with monoste'arin. Said amino carboxylic acid esters correspond to the formulae:

1 1"; calamar -omit? Example B 20 grams of the hydrochloride ofalpha amino.- acetyl chloride are reacted with"42 r'ams of monolaurin under substantially the samev conditions as are set out hereinabcve in Example A.

,.The reaction product.obtained .contain a mix- 1.

tur e .-th e" h:ydrochlpr des ofi the1mono-..anddi-.. glycin esters lof rnonolaurin, .Lsaid; vJcompo nds 7 having the formulae:

I mac-i ...crig-amenTa 11?s.-

car--0 ecu-ne i It will be understood that thesubstances may,

for certain purposes, beemployed 'in the form of impure reaction mixtures containing substantial proportions of thezefi'ective-compounds. Where the substances are used for bactericidal, germicidal and like purposes, however, purification procedures may be employed to produc pure or subform at 50-60 degrees C, and: to -the-;1:esultingt .-:v

stantially pure products. sThose-versed in the art are familiar with the types of .purification methods which may be employedwithiadvantage herein, particularly in the light of the-disclosures made hereinabove, r

in the general'formula maybe derived from various sources. Among such sources may be'mentioned the straight chain and. branched chain,

saturated and unsaturated,- carboxylic, aliphatic (including cycloaliphatic), fatty, aromatic, hydroaromatic, and araliphatic acids including acetic acid, propionic acid, butyric acid, caproic acid, pimelic acid, caprylic acid, capric acid, sebacic acid, behenic acid, arachidic acid, cerotic acid, erucic acid, melissic acid, stearic acid, oleic acid, ricinoleic acid, ricinelaidic acid, ricinostearolic acid, linoleic acid, linolenic acid, lauric acid, myristic acid, palmitic acid, mixtures of any two or more of the above mentioned acids or other acids, mixed higher fatty acids derived from animal or vegetable sources, for example, lard, coconut oil, rapeseed oil, sesame oil, palm kernel'oil, palm oil, olive oil, corn oil, cottonseed oil, sardine oil, tallow, soya bean oil, peanut oil, castor oil, seal oils, whale oils, shark oil and other fish oils, partially or completely hydrogenated animal and vegetable oils such as those mentioned; oxidized hydroxy and alpha-hydroxy higher carboxylic, aliphatic and fatty and/or polymerized higher fatty acids or higher fatty acids derived from oxidized and/or polymerized triglyceride oils; acyloxy carboxylic acids such as acids such as i-hydroxy stearic acid, dihydroxypalmitic acid, dihydroxy-stearic acid, dihydroxybehenic acid, alpha-hydroxy capric acid, alphahydroxy stearic acid, alpha-hydroxy palmitic acid, alpha-hydroxy lauric acid, alpha-hydroxy myristic acid, alpha-hydroxy coconut oil mixed fatty acids, alpha-hydroxy margaric acid, alphahydroxy arachidic acid, and the like; fatty and similar acids derived from various waxes such as beeswax, spermacetic, montan wax, coccerin, and carnauba wax and higher molecular weight carboxylic acids derived, by oxidation and other methods, from paraffin wax, petroleum and similar hydrocarbons; resinic and hydroaromatic acids such as hexahydrobenzoic acid, naphthenic acid and abietic acid; araliphatic and aromatic acids such as phthalic acid, benzoic acid, Twitchell fatty acids, naphthoic acid, pyridine carboxylic acid; hydroxy aromatic acids such as salicylic acid, hydroxy benzoic and naphthoic acids, and the like. any two or more of said acids may be employed if desired and it will also be appreciated that said acids may contain substituent groups such as sulphate, sulphonic, nitrile, cyanogen, carbonyl, amide, amine, halogen, ketone and other groups. in the form of their anhydrides, esters including mono-, ditri-glycerides and the like, and acyl halides, or, in general, in the form of any of their acylating compounds. Of particular utility, where the final compounds are used as'antiseptics, bactericides, germicides and the like, are the unsubstituted fatty acids, containing from eight to fourteen carbon atoms and their acyl halides, lauric acid or its acyl halide or coconut oil mixed fatty acids or their acyl halides being especially satisfactory.

The amino-carboxylic acids which are or may be utilized in the preparation of the substances include, among those previously mentioned and It will be understood that mixtures of phates, nitrates, hydrobromides, hydroiodides,

The acids may be employed as such or V others, alpha-amino acetic 1 .acid, alpha-amino propionic ,acid, alpha-amino butyric acid, betaamino butyric, acid, alphar'amino-n val'eric acid, alpha-amino, isobutyricacid, valphaeamino iso 'valericacid, Lphenylalanine, tyrosine; tryptophane, cystine, arginine, amino poly-carboxylic acids such as aminosuccinic acid, .amino glutaric acid, amino citric acid, amino malonic acid, amino adipic acid, amino sebacic acid, and the like; the amino-carboxylic acids or mixtures thereof obtained by the hydrolysis of proteins or protein-containing materials such as gluten, soya bean flour and :the' like, whetherby enzymatic action, by acids or by any. othermeans. Other amino-carboxylic acids include the synthetic polypeptides as well as those resulting from the hydrolysis of proteins or protein-containing materials. Illustrative examples of such polypeptides are glycyl-glycine and leucyl-glycyl-glycine. It

will be understood that mixtures of any two or more of the foregoing or other amino-carboxylic acids may be utilized in the preparation of the substances of the present invention. It will also be understood that any of these amino-carboxylic acids may be esterified with any of the monoglycerides disclosed hereinabove.

As indicated hereinabove, the compounds are best used in the form of salts, preferably in the form of substantially neutral salts or at a pH of about 6.7. The hydrochlorides are especially satisfactory but other salts may be employed, in certain instances, such as the sulphates, phospropionates, gluconates, sulphoacetates, sulphosuccinates, lactates, tartrates, citrates, salts of amino-carboxylic acids, and the like. The free esters of the amino-carboxylic acids generally possess limited solubility in water and, for that reason, the esters are used in the form of their salts, the salts possessing substantially greater water solubility. It is, however, within the broader scope of the invention to employ the free esters, using solvent media other than water or water alone, or by solubilizing the esters in any desired manner.

It will be understood that the numerous compounds disclosed herein will vary somewhat in bactericidal, germicidal, preservative, medicinal, bacteriostatic, antiseptic and fungicidal power or potency and that the effects will also vary depending upon the environment in which the compounds are used. The compounds are employed particularly in dilute aqueous or modified aqueous solutions, usually on the order of 0.1% to several thousandths of 1%. They may be used internally or externally and either as such or in conjunction with other agents having bactericidal, germicidal, antiseptic or like action. Particularly satisfactory use is in connection with dentifrices such as tooth powders, tooth pastes, liquid dentifrices, and mouth washes. In such cases, the proportions of the salts of the esters may, if desired, be somewhat higher than those set forth hereinabove. Their especial utility in dentifrices resides not only in the fact that they possess bactericidal, germicidal, and similar properties but,

in addition, they are innocuous, non-toxic and =tive against Jpneumoccc'cus." "In addition, the

phenol :coeflicients of many cf the cbmpounds are \substantially higher than that art phenol.

The term higher, as used herein and in the claims to describe carboxylicz'zmd fatty acids and the like, will be understcodjztoimean at ieaLst eight carbon atoms unless otherwise specifically stated. w i

1 Wherever the 'term ar'nino-carboxylic.acid'esters or like expression is employed "in the claims, 10

it will be understood to' cover the compe'unds'irrespectiv of whether they are neutralized :to form salts or are present as thfreebase; v

While the invention has been described in de- "tail, it is to be unders'toodfthat "the scope thereof is not to be limited other than is set forth in the claims.

What I claim as new and desire to protect by 5 Letters Patent of the United states is:

' 1 Alpha airiinbisobutyricacid'esters of meno- BENJAMIN R. HARRIS. 

